Really Rapid Review -- IAS 2011 Rome

Paul E. Sax, M.D., is director of the HIV Program and Division of Infectious Diseases at Brigham and Women's Hospital in Boston.

Just back from IAS 2011 (which was followed, I'm thrilled to say, with a visit to perhaps the most beautiful region in the world). Here is a Really Rapid ReviewTM of the meeting, with apologies ahead of time for lack of organization and (even more likely) leaving out something important. FYI, the abstracts are online here; I'm sure there's a place on the meeting homepage that has the same link, but I can't seem to find it.

All 052, all the time. This landmark study was the big story at the conference, with several presentations on it (and the paper published the same day in the NEJM; Journal Watch comment here). Very interesting fact: the only linked transmission in a person whose partner was randomized to early therapy probably took place before virologic suppression. At the end of the series of talks on the study -- which covered the primary outcome, details on how they documented viral linkage, and the clinical, immunologic, and virologic results -- the investigators (led by Mike Cohen) received a standing ovation from the audience. Well deserved. (Quick aside: Did they ever tell the participants whether the HIV transmission was linked to the infected partner? I suspect not, but ...)

What about PrEP? Results from two favorable studies (abstract here for one, slides here for the other) were released just before the conference, and further details were presented right after the 052 data. Important studies? Yes. "Game changers" for clinical practice, like 052? Probably not.

Dolutegravir looks really, really good. Week 48 data from a relatively large phase II naive study show around a 90% suppression rate, no obvious toxicity, and -- amazingly -- no integrase-inhibitor resistance among virologic failures. Could dolutegravir be like a boosted PI in that regard? This smart guy thinks so. In an odd coincidence of recent HIV drug development, dolutegravir seems to do the same thing with inhibition of creatinine secretion (thereby raising serum creatinine without reducing GFR) as cobicistat.

Speaking of integrase inhibitors, once-daily elvitegravir is "non-inferior" to raltegravir in treatment-experienced patients. Good news, as the phase II study of elvitegravir was highly problematic, in hindsight due to both dosing issues and the absence of active background therapy. Note that in this phase III study, elvitegravir was given with a PI boosted by ritonavir, not by cobicistat. And cobicistat sounds great with an Italian accent.

Any other promising new investigational drugs out there? Maybe -- The NNRTI lersivirine was almost as good as efavirenz in this phase II study. Since phase II studies tend to be relatively small, any signals of inferior efficacy are necessarily a concern.

In a similar vein, the two-drug regimen of ATV/r and QD maraviroc was (again) almost as good as ATV/r + TDF/FTC. Specifically: More hyperbilirubinemia in the maraviroc arm and also more low-level viremia. Since the population had to have a CD4 > 100 and R5 virus, the bar was not set very high for successful treatment. Could three drugs be required for optimal efficacy no matter what?

Week 96 data on TDF/FTC + rilpivirine show pretty much what we saw at week 48 (published in this issue of The Lancet): More virologic failure with rilpivirine (especially at high viral loads), but more issues around tolerability/lipids with efavirenz. An open-label study of the two single-pill options using these drugs -- Atripla (TDF/FTC/EFV) vs. so-called B-tripla (TDF/FTC/RPV) -- is ongoing.

What happens if you take 311 patients stable on ABC/3TC + a boosted PI and randomize half of them to change the NRTIs to TDF/FTC? Yes, lipids improve and estimated GFR worsens, but there's also something surprising: fewer virologic failures (3 vs. 11). All low-level virologic rebounds, but still -- perhaps the results are telling us something about the relative potency of these two NRTI combinations.

We've known for some time that tenofovir-based treatments reduce bone-mineral density more than comparators, but what are the clinical sequelae?In this large VA-based study, tenofovir exposure was associated with a small but statistically significant risk of osteoporotic fractures (hazard ratio after controlling for everything, 1.12).

Do boosted PIs increase the risk of chronic kidney disease?Perhaps some of them -- notably ATV/r and LPV/r -- do, according to these three studies (one, two -- abstract says DRV/r, poster didn't -- and three). Is this mediated through their effect on tenofovir levels or some other mechanism?

Treating acute HIV infection for 48 weeks delayed CD4 decline more than treating for only 12 weeks or not at all. Viral "set point" after stopping treatment was also lower in the 48-week treatment group, with a greater beneficial effect seen if therapy was started closer to seroconversion. Since this was a randomized trial, and since treatment interruption has looked pretty bad in every recent study, are we ready to say that all patients with acute HIV should be treated? I think we're very close, if not there already.

Does a regimen's "CPE" (CNS penetration effectiveness) score improve neuropsychologic function? Not according to this study. Data in this area are so conflicting that one almost needs to be a top performer on neuropsych tests just to keep the studies straight.

With d4T use being phased out worldwide, the four WHO-recommended initial regimens all consist of tenofovir, 3TC or FTC, and either efavirenz or nevirapine. According to this presentation, TDF/3TC/NVP could be suboptimal, with high rates of virologic failure and emergent drug resistance (especially K65R). Given that this regimen is probably the cheapest and thus the most likely to be implemented widely, confirming its effectiveness is absolutely critical.

A few final words about the conference: The weather was beautiful (one shudders to think what next summer in Washington DC will be like), Rome is extraordinary (so long as you can dodge all the scooters and Fiats zipping around), and I bet all 7,482 participants ate very, very well. Certainly I did.

But did the posters have to be displayed in a converted parking garage?

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